Podcast Transcript

Cutting chromosomes gives clues to cell division

When we need new cells in our body, for example, to replace dead or damaged cells, they don't just appear from nowhere – they are created by the division of one cell into two new daughters. This process is called mitosis. Now scientists at the University of Michigan have used a clever laser technique to get an even closer insight into how mitosis works, and how it might go wrong in diseases like cancer, where cells divide out of control. 

Normally in mitosis, cells copy all their DNA, then line up these two sets of chromosomes in the middle of the cell, thanks to a microscopic scaffold-like structure called the spindle. The spindle grows from each side of the cell, and attaches to the chromosomes, eventually pulling them apart in opposite directions. If this goes wrong, then the new daughter cells may end up with the wrong number of chromosomes, which is bad news for the cell.  

For many years, researchers have tried to understand how the cell manages to divide its chromosomes equally between daughters, and now new research in this week's edition of Current Biology by Alan Hunt and his team may help to explain why. The Michigan team used high speed lasers to slice off tiny pieces of chromosomes from within living, dividing newt cells, and watched what happened. The pulses of laser light lasted for only a femtosecond -a billionth of a millionth of a second, but they were enough to cut the chromosomes. 

Previously, researchers have though that something called 'polar ejection forces' are at working in dividing cells, helping to maintain the pull across the spindle, and ensure that an equal number of chromosomes go to each new cell. Hunt suspected that these forces should be directly related to  the size of the chromosomes, so cutting off measurable pieces should have proportionally measurable effects on cell division – and that's what they found. They also discovered that these polar ejection forces are an important physical cue that helps to directly control mitosis, and the direction of chromosome movements.

Not only does this discovery shed light on cancer – and on chemotherapy, which often works by blocking mitosis in cancer cells – but it could also help us to understand genetic diseases such as Down's Syndrome, which are caused by an incorrect number of chromosomes during egg formation.

31st May 2009

The oldest known leper

This week scientists have uncovered what they think is the world’s oldest example of a leprosy victim.  This is a paper in the journal PLoS One and the pictures are absolutely stunning; to an osteoarchaeologist at least.

Gwen Robins and her colleagues, based at the Appalachian State University in North Carolina, have been working at a site in North-West India called Balathal.They have excavated a site which can be very quite reliably dated to about 2000BC, so 4000 years ago. There they’ve found the remains of a 37 year-old man, identified by looking at the shape of the pelvic bones, because men have different-shaped pelves to women. 

This skeleton shows bone changes which are very characteristic of leprosy.  If you look at the skull you can see what’s called reactive flare on the surface coating of the bone above one of the eye sockets.  There’s also a complete hole in the bone adjacent to the underside of the nose and there’s also damage under one of the eye sockets and degeneration in the backbone.

For a long time people have said that there are a number of diseases that will cause similar bony changes like these: syphilis is one of them, osteomyelitis and tuberculosis are others. The reason this seems a good candidate for leprosy is because a) we can place it in space and time and b) it coincides with what we know people were doing at that time. There are historical records that go back to within 500 years of this: these are Sanskrit hymns which talk about an apparently similar disease. But until now there hasn’t been any archaeological evidence to back it up.

It also coincides with what we know people were doing at this time.  One theory suggests leprosy originated originally in Africa and as people migrated out of East Africa perhaps they took it with them. Another theory suggests it didn’t originate there at all and that it could have originated where this person was found, in India.  This body is a really important discovery because it coincides with early populations moving from nomadic hunter-gatherers to villages and towns supported by agriculture and keeping animals. They were therefore living more closely together and facilitating the spread of the disease. Leprosy is very low-infectivity but it is nonetheless an infectious illness. It needs people to be in close contact because only a small minority of the population are susceptible. You need a big population living together to get enough people spreading it around otherwise it would just die out.

31st May 2009

Fatty acids affect genes

We hear a lot about good fats and bad fats, and it can all get a bit confusing.  Now researchers in the US have studied the effects off the ratio of different fats in humans, and their effects on gene activity.

Over the past century, we've seen significant changes in our Western diet, including a shift in the ratio of certain fats, as omega 6 and omega 3 fatty acids. Omega 6 fats are usually found in meat and vegetable oils, while omega 3 come from flax and fish oils.  Many researchers have suggested that this shift in fat ratios is contributing to bad effects on human health, including inflammation, which is a key player in autoimmune diseases and allergies, and even conditions such as diabetes and arthritis.

Now researchers  led by Floyd Chilton, writing in the Journal of Biological Chemistry, have carried out a study using human volunteers on a controlled diet, to try and understand how changes in this fat ratio might affect our bodies.

Evidence from history suggests that our ancestors lived on a 2 to 1 ratio of omega 6 to omega 3 fats, but in recent years our Western diet has a ratio of around 10 to 1. The researchers took 27 healthy volunteers, and fed them on a controlled diet containing a 2 to 1 ratio of omega 6 to omega 3 fats, then measured the activity of certain genes and markers of inflammation and immune actitivity. The team found a  significant drop in the levels of important molecules involved in inflammation, including an important inflammation protein called PI3K, which plays a crucial early role in inflammation.

Although this is only a very small study, and much more work needs to be done, the results are a tantalising suggestion of how the ratio of fats we eat could be affecting our gene activity, and increasing our risk of inflammation and other diseases. So watch this space.

31st May 2009

Freeze on oil

American researchers have discovered that the Arctic Circle may contain as much as 30% of the world's undiscovered natural gas deposits and upto 13% of undiscovered oil, or double what we first thought. Writing in the journal Science, US Geological Survey (USGS) scientist Donald Gautier and his colleagues have used geological data, including information provided by petroleum companies, to make predictions about the locations and quantities of oil and gas reserves north of the Arctic Circle.

They began by first geologically dividing up the area, which covers 6% of the planet's surface, and singling out 49 hotspot regions termed assessment units (AUs). These were areas that contained the appropriate types of sedimentary rocks more than 3km thick, the minimum rock depth thought to be required to bury petroleum-bearing source rocks sufficiently to produce oil. Onto this map the team then superimposed data about the source rock types, migration pathways and other geological configurations that alter the prospects of finding oil in a given location. They then compared these findings with similar results compiled from 246 other oil-bearing locations worldwide in order to make predictions about the chances of each of the Arctic areas containing appreciable reserves.

The results suggest that between 22 billion and 256 billion barrels of oil lie undiscovered underneath the Arctic, which is more than double what's previously been discovered there and might account for up to 4% of the world's remaining oil and 13% of the remaining undiscovered oil. To put these numbers into perspective, current estimates suggest that the World burns 30 billion barrels of oil per year and there are about 1240 billion barrels remaining globally. At worst, the Arctic could probably sate the populations thirst for oil for at least one year.

As well as oil the models also predict prodigious natural gas deposits at least three times greater in energy terms than the oil reserves. Most of this gas is in Russian territory which, say the researchers, could "reinforce the preeminent strategic resource position of that country," if they exploit it. Either way, tough decisions need to be taken regarding the recovery of Arctic oil given the environmental costs, both of obtaining it and when it is burned.

31st May 2009

A plethora of skin bacteria

Chris -   Now also in the news this week, researchers have discovered a far more diverse collection of bacteria living on our skin than we thought was possible before, and it turns out that it’s not just our good old friend Staph aureus, or other species of Staphylococcus that lay claim to our bodily surfaces.  To tell us a bit more, here is Julie Segre, hello Julie...

Julie Segre - Hello.

Chris -   Welcome to the Naked Scientists.  You’ve published this wonderful paper in Science this week about this, how did you go about mapping what bugs were living on who and where?

Julie Segre -   Well it’s really quite straightforward because the skin is so accessible, so we asked healthy volunteers to come in to the NIH clinical centre, and we took something that looks very much like a Q-tip and we swabbed the bacteria off the different parts of their body, everything from their forehead to behind their ear to behind their knees to underneath their foot and between their fingers, and then instead of culturing these in the lab, which has been our traditional method for knowing what bacteria reside on the skin, we sequenced the DNA immediately.  So there was no culturing, we just looked at the signature of each bacteria by it’s DNA sequence, and those sequences are unique enough that we could say ‘this is a staphylococcus, this is a streptococcus, this is a Corynebacterium', and we found an enormous diversity of bacteria that we really hadn’t appreciated before.

Chris -   Because when you put things in culture, of course, there’s a selection applied, in other words, some things won’t grow in culture, so scientists will have missed them before, but by using genetic techniques, you’re able to see what we couldn’t see before.  How are you then going to take that further, what can you tell us about the spectrum of bugs that are on the body’s surface and how they might be linked to various diseases, for instance?

Julie Segre -   Well this is a baseline, and studied that were done previously that were based on culture really gave us an incomplete view.  Now some of these bacteria, actually, now that we know we’re looking for a Pseudomonas or we’re now looking for a Corynebacterium, we can now culture them.  And the interesting thing about culturing bacteria is it’s very hard to know what you don’t know, but it’s easy to find what you are looking for.  So now we tailor the media, for example a lot of the bacteria live on the oily surfaces of our skin, and when we add, we really just add lipids or oil to the culture broth, now we can grow these bacteria – we just didn’t know they were there before.  This gives us a baseline so now we can begin to examine eczema, psoriasis, acne, we can begin to ask what is different?  Besides even what we can culture in the lab, how has the microflora changed, and then how do we have tailored therapies to being it back into balance?

Chris -   Because some people have suggested that some of those skin conditions that you cite are aggravated by the presence of bacteria, and that in fact they drive or stimulate the condition and make it worse.  It’s not so much that it’s just because there’s damaged skin there, it’s the combination of some damaged skin, which gets these bacteria in there in the first place, and then they make the problem worse.

Julie Segre -   That’s absolutely right.  Something like eczema has a very strict connection with a Staphylococcus aureus infection.  Then there are other diseases like the MRSA, the Methicillin-resistant Staph aureus, we know that’s a bacterial infection, but we also know that a lot of people have a small, tiny, tiny amount of MRSA that you could find in their nose – they never get an infection.  So we’re suggesting that it might be the healthy bacteria, the commensals, that keep those pathogenic bacteria in check.

Chris -   I was just going to say, because, we have come around to the idea in recent years that having a healthy intestinal bug spectrum helps to protect us from various things, if you go to a foreign country and you don’t get travellers' diarrhoea because you have a healthy microbial flora, could the same be true of the skin, and in fact people in whom there is some kind of problem with their normal skin bacteria, it makes them more prone to getting infections that a person who doesn’t have that problem with their skin flora wouldn’t get?

Julie Segre -   That’s such an interesting idea to pursue, because its’ interesting from the perspective of science, I think that’s absolutely right on and that’s where we’re going to go with these experiments – to understand maybe why someone has a predilection for developing a skin disorder based on a change in their microflora.  It’s also interesting from a societal perspective – why is it that we want to eat prebiotics and balance our gut microflora, but we want to sterilise the outside of our bodies?  We have to realise that there are healthy bacteria that live on our skin, and that we need to promote their growth.  I’m not talking about letting everything grow on your skin, there are a lot of transient bacteria that are bad, and I’m a deep believer in personal hygiene – washing your hands, using soap and all sorts of products.  I think there’s a great use for all sorts of skincare products, but I also think that we have to realise that the goal is balance.

Chris -   I was just going to say, Julie, have you been in the shower this month?! No, I’m just joking, but basically the way forward now is to begin to say how do we tie different bacterial populations to different diseases or lack of diseases, can we understand more about what’s healthy.  In the long run, perhaps we’re going to see skin crèmes that are not designed to abolish bacteria, but to encourage the ones we do want, not the ones we don’t.

Julie Segre -   Absolutely, and I think there are also intrinsic changes to our skin, the skin of a baby is not the skin of a teenager, is not the skin of an older person, so we have to understand that these things change with time, and that as we change the environment in which we live, we may be altering the microflora.  I think these are going to have profound effects on both common and rare skin disorders.

Chris -   Julie, we’re going to have to leave it there, thank you very much for joining us.  

Julie Segre -   Thank you so much.

Chris -   That was Julie Seagre, who is from the National Human Genome Research Institute in the US, she’s got a paper in Science this week in which she sets out basically what’s living on you.

May 2009

This Week in Science History - Identifying AIDS

This Week in Science History saw, in 1981, the publication of an article that was the first to describe a new endemic disorder of the immune system – what would later become known as Auto Immune Deficiency Syndrome, or AIDS.

The paper was published by Michael Gottlieb through the American Centre for Disease Control and Prevention (the CDC) and was the first report of a disease that is now estimated to have killed over 25 million people since 1981. Death is usually caused by opportunistic infections that take advantage of the body’s reduced immune system – such as pneumonia.

At the time, Gottlieb was working at the UCLA Medical Centre, and the groups of symptoms shown by the homosexual men he examined did not fit any known disease. These included diarrhoea, fever, swollen lymph nodes and thrush infections in the mouth, something which often occurred in patients known to have reduced T lymphocyte numbers.

These cells are the part of the immune system that ‘seek and destroy’ invading pathogens like viruses and bacteria. Tests on Gottlieb’s patients confirmed they had a very low T cell count, particularly the T cells with a marker on their surface known as CD4.

Other symptoms included a particular form of pneumonia also seen in immuno-deficient children and Kaposi’s sarcoma, a form of skin cancer also related to reduced immune function.

Since then, many other symptoms have been recognised, since there are many infections that can take hold in AIDS sufferers.

Originally, the disease was not known as AIDS. The CDC referred to it by using the names of the associated infections such as ‘Kaposi’s Sarcoma and opportunistic infections’, but by the end of 1981, in the press it was known as GRID – Gay Related Immune Deficiency. However, in time it became apparent that not just homosexuals were affected, so in 1982, the name AIDS was coined and became the official name for the disease.

At this time, it was still not clear exactly what caused AIDS, but in 1983 and 84, two scientists, working in France and America respectively, isolated a virus from the lymph glands of individuals with AIDS and concluded that this virus was the cause of AIDS. There was significant controversy over the discovery of the virus, with each lab claiming to be the first to realise that this virus was the culprit, and it was not until 1986 that the name Human Immunodeficiency Virus was coined.

Gottlieb went on to be an important figure in AIDS research, being one of the first to trial AZT as a treatment. This drug is an antiretroviral drug and was the first drug approved to treat HIV infection. It is still used as part of the treatment today, combined with other antiretroviral drugs that slow the replication of the HIV virus in cells. These drugs can prolong life by 4-12 years for sufferers – without them, survival once AIDS develops is only around 9 months. However, these treatments are expensive and so are mainly only available in Western countries. In Sub-Saharan Africa, where around 2/3 of all AIDS sufferers live, these treatments are far too costly.

Unfortunately, there is as yet no cure for HIV as it has a very high mutation rate, meaning that once a drug is devised that will work on that particular strain, the virus has mutated and the drug will no longer work on it. Billions of dollars are spent each year trying to find a cure, but at the moment, the best cure is prevention, with global campaigns to increase condom use, and centres where drug addicts can pick up clean needles to reduce HIV spread.

Gottlieb’s paper was the first from the medical community to suggest that this disease was something serious and far reaching, and since its publication, our understanding of HIV and AIDS has greatly increased. The story does not have a happy ending yet, and we have many years of medical research ahead of us before we can see an end to this disease.

June 2009